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Emergence of the Zika virus Asian lineage in Angola

Sarah C. Hill, Jocelyne Vasconcelos, Zoraima Neto, Domingos Jandondo, Líbia Zé-Zé, Renato Santana Aguiar, Joilson Xavier, Julien Thézé, Marinela Mirandela, Ana Luísa Micolo Cândido, Filipa Vaz, Cruz dos Santos Sebastião, Chieh-Hsi Wu, Moritz Kraemer, Adriana Melo, Bruno L.F. Schamber-Reis, Girlene S. de Azevedo, Amilcar Tanuri, Luiza M. Higa, Carina Clemente, Sara Pereira da Silva, Darlan da Silva Candido, Ingra M. Claro, Nurse Domingos Quibuco, Cristóvão Domingos, Bárbara Pocongo, Alexander G. Watts, Kamran Khan, Luiz Carlos Junior Alcantara, Ester C. Sabino, Eve Lackritz, Oliver G. Pybus, Maria-João Alves, Joana Afonso, Nuno R. Faria
doi: https://doi.org/10.1101/520437
Sarah C. Hill
1Department of Zoology, University of Oxford, U.K.
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Jocelyne Vasconcelos
2Instituto Nacional de Investigação em Saúde, Ministry of Health, Luanda, Angola.
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Zoraima Neto
2Instituto Nacional de Investigação em Saúde, Ministry of Health, Luanda, Angola.
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Domingos Jandondo
2Instituto Nacional de Investigação em Saúde, Ministry of Health, Luanda, Angola.
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Líbia Zé-Zé
3Instituto Nacional de Saúde Doutor Ricardo Jorge, Águas de Moura, Portugal.
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Renato Santana Aguiar
4Departamento de Genética, Instituto de Biologia, Universidade Federal do Rio de Janeiro, Brazil.
5Departamento de Biologia Geral, Instituto de Ciências Biológicas, Universidade Federal de Minas Gerais, Brazil.
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Joilson Xavier
6FioCRUZ Rio de Janeiro, Brazil.
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Julien Thézé
1Department of Zoology, University of Oxford, U.K.
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Marinela Mirandela
2Instituto Nacional de Investigação em Saúde, Ministry of Health, Luanda, Angola.
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Ana Luísa Micolo Cândido
2Instituto Nacional de Investigação em Saúde, Ministry of Health, Luanda, Angola.
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Filipa Vaz
2Instituto Nacional de Investigação em Saúde, Ministry of Health, Luanda, Angola.
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Cruz dos Santos Sebastião
2Instituto Nacional de Investigação em Saúde, Ministry of Health, Luanda, Angola.
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Chieh-Hsi Wu
7Department of Statistics, University of Oxford, U.K.
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Moritz Kraemer
1Department of Zoology, University of Oxford, U.K.
8Computational Epidemiology Lab, Boston Children’s Hospital, Boston, USA.
9Harvard Medical School, Boston, USA.
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Adriana Melo
10Instituto de Pesquisa Professor Joaquim Amorim Neto (IPESQ), Campina Grande, Brazil.
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Bruno L.F. Schamber-Reis
11Department of Human Genetics, Centro Universitário Unifacisa, Campina Grande, Brazil.
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Girlene S. de Azevedo
10Instituto de Pesquisa Professor Joaquim Amorim Neto (IPESQ), Campina Grande, Brazil.
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Amilcar Tanuri
4Departamento de Genética, Instituto de Biologia, Universidade Federal do Rio de Janeiro, Brazil.
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Luiza M. Higa
4Departamento de Genética, Instituto de Biologia, Universidade Federal do Rio de Janeiro, Brazil.
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Carina Clemente
12Cligest Clinic, Luanda, Angola.
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Sara Pereira da Silva
12Cligest Clinic, Luanda, Angola.
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Darlan da Silva Candido
1Department of Zoology, University of Oxford, U.K.
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Ingra M. Claro
13Instituto de Medicina Tropical e Faculdade de Medicina da Universidade de São Paulo, São Paulo, Brazil.
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Nurse Domingos Quibuco
14Hospital Pediátrico David Bernardino, Luanda, Angola.
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Cristóvão Domingos
15Instituto Nacional de Luta Contra SIDA, Luanda, Angola.
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Bárbara Pocongo
15Instituto Nacional de Luta Contra SIDA, Luanda, Angola.
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Alexander G. Watts
16Li Ka Shing Knowledge Institute, St. Michael’s Hospital, Toronto, Canada.
17BlueDot, Toronto, Canada.
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Kamran Khan
16Li Ka Shing Knowledge Institute, St. Michael’s Hospital, Toronto, Canada.
17BlueDot, Toronto, Canada.
18Department of Medicine, University of Toronto, Canada.
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Luiz Carlos Junior Alcantara
6FioCRUZ Rio de Janeiro, Brazil.
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Ester C. Sabino
13Instituto de Medicina Tropical e Faculdade de Medicina da Universidade de São Paulo, São Paulo, Brazil.
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Eve Lackritz
19World Health Organization, Switzerland, Geneva.
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Oliver G. Pybus
1Department of Zoology, University of Oxford, U.K.
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Maria-João Alves
3Instituto Nacional de Saúde Doutor Ricardo Jorge, Águas de Moura, Portugal.
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Joana Afonso
2Instituto Nacional de Investigação em Saúde, Ministry of Health, Luanda, Angola.
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  • For correspondence: jmafonso.7@gmail.com nuno.faria@zoo.ox.ac.uk
Nuno R. Faria
1Department of Zoology, University of Oxford, U.K.
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  • For correspondence: jmafonso.7@gmail.com nuno.faria@zoo.ox.ac.uk
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Abstract

Evidence before this study We searched PubMed without language restrictions using the keywords ‘Zika’ and ‘Africa’ for papers published to October 2018. We also checked available ‘Situation Report’ publications from WHO for evidence of Zika virus (ZIKV) or congenital Zika disease in Africa. ZIKV African lineage has been detected within Africa since the mid 20th century, yet evidence for spread of the ZIKV Asian lineage within Africa is limited. Two countries in Africa (Cabo Verde and Angola) have reported ZIKV cases that are believed to be caused by a newly introduced Asian lineage virus. Sequence data are critical for confirming and understanding the spread of ZIKV Asian lineage within Africa, but these data are currently limited to a single 193bp fragment of the ZIKV NS1 gene from Angola. In addition, whilst epidemiological data on ZIKV and suspected microcephaly cases have been reported in detail from Cabo Verde, data from Angola are extremely limited.

Added value of this study We provide a detailed report of detected ZIKV acute cases and suspected microcephaly cases in Angola. We sequence ZIKV genomes from three acutely infected cases. These represent the first three Asian lineage genomes available from Africa, one of which was acquired from a baby with confirmed microcephaly. Analysis of these sequences suggests that ZIKV may have been introduced to Angola between July 2015 and June 2016, after which it likely circulated for at least one year. This provides the first genetic confirmation of autochthonous ZIKV Asian lineage transmission within Africa. We suggest that the virus was more likely introduced to Angola directly from Brazil, rather than from Cabo Verde. Our analyses from Angola, only the second African country to report presence of the Asian virus lineage, therefore improve our understanding of the extent and clinical impact of ZIKV Asian lineage in the continent.

Implications of all the available evidence The circulation of ZIKV Asian lineage within parts of sub-Saharan Africa is concerning given the potential for continued viral spread across much of the continent. Available evidence suggests that ZIKV has circulated and caused cases of microcephaly in Cabo Verde and in Angola. Detecting additional ZIKV transmission using only clinical data on suspected microcephaly or clusters of mild illness may be challenging in countries where systems for reporting birth defects are limited and infectious disease burden is high. Further spread of the ZIKV Asian lineage would likely not be detected unless molecular surveillance systems for ZIKV are implemented to routinely monitor ZIKV transmission in Africa. Implementation of such a surveillance system is especially important in countries that are linked by high human mobility to areas that have experienced recent or ongoing outbreaks of ZIKV.

Background Zika virus (ZIKV) infections and suspected microcephaly cases have been recently reported in Angola, but no data are available on the origins, epidemiology, and diversity of the virus.

Methods Serum samples from 54 suspected ZIKV cases, 76 suspected microcephaly cases, and 24 mothers of infants with suspected microcephaly were received by the Angolan Ministry of Health. Computed tomographic brain imaging and serological assays (PRNT) were conducted on one microcephalic infant. All sera were tested for ZIKV by RT-qPCR. 349 samples from HIV+ patients and 336 samples from patients suspected of chikungunya virus or dengue virus infection were also tested. Portable sequencing was used to generate Angolan ZIKV genome sequences, including from a ZIKV+ neonate with microcephaly born in Portugal to an Angolan resident. Genetic and mobility data were analysed to investigate the date of introduction and geographic origin of ZIKV in Angola.

Findings Four autochthonous cases were ZIKV positive via RT-qPCR, with all positive samples collected between December 2016 and June 2017. Viral genomes were generated for two of these cases, and from the neonate with microcephaly identified in Portugal. Genetic analyses and other data indicate that ZIKV was introduced to Angola from Brazil between July 2015 and June 2016. This introduction likely initiated local ZIKV circulation in Angola that continued until June 2017. The scanned microcephaly case showed brain abnormalities consistent with congenital Zika syndrome and serological evidence for maternal ZIKV infection.

Interpretation Our analyses confirm the autochthonous transmission of the ZIKV Asian lineage in continental Africa. Conducting ZIKV surveillance throughout Africa is critical in the light of presented evidence for autochthonous ZIKV transmission in Angola, and associated microcephaly cases.

Funding Royal Society, Wellcome Trust, CNPq, CAPES, ERC, Oxford Martin School, Global Challenges Research Fund, Africa Oxford, and John Fell Fund.

Copyright 
The copyright holder for this preprint is the author/funder, who has granted bioRxiv a license to display the preprint in perpetuity. It is made available under a CC-BY-NC-ND 4.0 International license.
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Posted January 18, 2019.
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Emergence of the Zika virus Asian lineage in Angola
Sarah C. Hill, Jocelyne Vasconcelos, Zoraima Neto, Domingos Jandondo, Líbia Zé-Zé, Renato Santana Aguiar, Joilson Xavier, Julien Thézé, Marinela Mirandela, Ana Luísa Micolo Cândido, Filipa Vaz, Cruz dos Santos Sebastião, Chieh-Hsi Wu, Moritz Kraemer, Adriana Melo, Bruno L.F. Schamber-Reis, Girlene S. de Azevedo, Amilcar Tanuri, Luiza M. Higa, Carina Clemente, Sara Pereira da Silva, Darlan da Silva Candido, Ingra M. Claro, Nurse Domingos Quibuco, Cristóvão Domingos, Bárbara Pocongo, Alexander G. Watts, Kamran Khan, Luiz Carlos Junior Alcantara, Ester C. Sabino, Eve Lackritz, Oliver G. Pybus, Maria-João Alves, Joana Afonso, Nuno R. Faria
bioRxiv 520437; doi: https://doi.org/10.1101/520437
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Emergence of the Zika virus Asian lineage in Angola
Sarah C. Hill, Jocelyne Vasconcelos, Zoraima Neto, Domingos Jandondo, Líbia Zé-Zé, Renato Santana Aguiar, Joilson Xavier, Julien Thézé, Marinela Mirandela, Ana Luísa Micolo Cândido, Filipa Vaz, Cruz dos Santos Sebastião, Chieh-Hsi Wu, Moritz Kraemer, Adriana Melo, Bruno L.F. Schamber-Reis, Girlene S. de Azevedo, Amilcar Tanuri, Luiza M. Higa, Carina Clemente, Sara Pereira da Silva, Darlan da Silva Candido, Ingra M. Claro, Nurse Domingos Quibuco, Cristóvão Domingos, Bárbara Pocongo, Alexander G. Watts, Kamran Khan, Luiz Carlos Junior Alcantara, Ester C. Sabino, Eve Lackritz, Oliver G. Pybus, Maria-João Alves, Joana Afonso, Nuno R. Faria
bioRxiv 520437; doi: https://doi.org/10.1101/520437

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